Investigation of the pharmacokinetics of 3′-deoxy-3′-[18F]fluorothymidine uptake in the bone marrow before and early after initiation of chemoradiation therapy in head and neck cancer

Yusuf Menda; Laura L. Boles Ponto; Kenneth J. Dornfeld; Timothy J. Tewson; G. Leonard Watkins; Anjali K. Gupta; Carryn Anderson; Sarah McGuire; Michael K. Schultz; John J. Sunderland; Michael M. Graham; John M. Buatti

doi:10.1016/j.nucmedbio.2010.02.005

Investigation of the pharmacokinetics of 3′-deoxy-3′-[¹⁸F]fluorothymidine uptake in the bone marrow before and early after initiation of chemoradiation therapy in head and neck cancer

Yusuf Menda, Laura L. Boles Ponto, Kenneth J. Dornfeld, Timothy J. Tewson, G. Leonard Watkins, Anjali K. Gupta, Carryn Anderson, Sarah McGuire, Michael K. Schultz, John J. Sunderland, Michael M. Graham, John M. Buatti

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

Introduction: The kinetics of the bone marrow uptake of 3'-deoxy-3'-[¹⁸F]fluorothymidine (FLT) before and early after initiation of chemoradiation therapy was investigated in patients with head and neck cancer. Methods: Fourteen subjects with head and neck cancer underwent FLT positron emission tomography (PET) at baseline and after 10 Gy of radiation therapy. Thirteen subjects also received one cycle of platinum-based chemotherapy before the second FLT PET. Kinetic parameters, including the flux constant based on compartmental analysis (K_FLT) and the Patlak constant (K_Patlak) for cervical marrow, were calculated. Standardized uptake values (SUVs) for the cervical marrow (inside the radiation field) and lumbar spine marrow (outside the radiation field) were also determined. Results: There was a significant drop in FLT uptake in the bone marrow inside the radiation field. Mean pretreatment uptake values for the cervical spine were SUV=3.08±0.66, K_FLT=0.045±0.016 min^-1 and K_Patlak=0.039±0.013 min^-1. After treatment, these values were SUV=0.74±0.19, K_FLT=0.011±0.005 min^-1 and K_Patlak=0.005±0.002 min^-1. Compartmental analysis revealed a significant drop in k₃ in irradiated cervical marrow. FLT uptake in the bone marrow outside the radiation field exhibited a significantly smaller decrease. Conclusions: There is a marked decrease in FLT uptake in irradiated bone marrow after 10 Gy of radiation therapy to the head and neck. The drop in FLT uptake in irradiated marrow is due to a significant decrease in the net phosphorylation rate of FLT.

Original language	English (US)
Pages (from-to)	433-438
Number of pages	6
Journal	Nuclear Medicine and Biology
Volume	37
Issue number	4
DOIs	https://doi.org/10.1016/j.nucmedbio.2010.02.005
State	Published - May 2010

Keywords

3′-Deoxy-3′-[F]fluorothymidine
Bone marrow
Chemoradiation
FLT

ASJC Scopus subject areas

Molecular Medicine
Radiology Nuclear Medicine and imaging
Cancer Research

Access to Document

10.1016/j.nucmedbio.2010.02.005

Cite this

Menda, Y., Boles Ponto, L. L., Dornfeld, K. J., Tewson, T. J., Watkins, G. L., Gupta, A. K., Anderson, C., McGuire, S., Schultz, M. K., Sunderland, J. J., Graham, M. M., & Buatti, J. M. (2010). Investigation of the pharmacokinetics of 3′-deoxy-3′-[¹⁸F]fluorothymidine uptake in the bone marrow before and early after initiation of chemoradiation therapy in head and neck cancer. Nuclear Medicine and Biology, 37(4), 433-438. https://doi.org/10.1016/j.nucmedbio.2010.02.005

Investigation of the pharmacokinetics of 3′-deoxy-3′-[¹⁸F]fluorothymidine uptake in the bone marrow before and early after initiation of chemoradiation therapy in head and neck cancer. / Menda, Yusuf; Boles Ponto, Laura L.; Dornfeld, Kenneth J. et al.
In: Nuclear Medicine and Biology, Vol. 37, No. 4, 05.2010, p. 433-438.

Research output: Contribution to journal › Article › peer-review

Menda, Y, Boles Ponto, LL, Dornfeld, KJ, Tewson, TJ, Watkins, GL, Gupta, AK, Anderson, C, McGuire, S, Schultz, MK, Sunderland, JJ, Graham, MM & Buatti, JM 2010, 'Investigation of the pharmacokinetics of 3′-deoxy-3′-[¹⁸F]fluorothymidine uptake in the bone marrow before and early after initiation of chemoradiation therapy in head and neck cancer', Nuclear Medicine and Biology, vol. 37, no. 4, pp. 433-438. https://doi.org/10.1016/j.nucmedbio.2010.02.005

@article{c258fee16ca04182a5e65768a1633b79,

title = "Investigation of the pharmacokinetics of 3′-deoxy-3′-[18F]fluorothymidine uptake in the bone marrow before and early after initiation of chemoradiation therapy in head and neck cancer",

abstract = "Introduction: The kinetics of the bone marrow uptake of 3'-deoxy-3'-[18F]fluorothymidine (FLT) before and early after initiation of chemoradiation therapy was investigated in patients with head and neck cancer. Methods: Fourteen subjects with head and neck cancer underwent FLT positron emission tomography (PET) at baseline and after 10 Gy of radiation therapy. Thirteen subjects also received one cycle of platinum-based chemotherapy before the second FLT PET. Kinetic parameters, including the flux constant based on compartmental analysis (KFLT) and the Patlak constant (KPatlak) for cervical marrow, were calculated. Standardized uptake values (SUVs) for the cervical marrow (inside the radiation field) and lumbar spine marrow (outside the radiation field) were also determined. Results: There was a significant drop in FLT uptake in the bone marrow inside the radiation field. Mean pretreatment uptake values for the cervical spine were SUV=3.08±0.66, KFLT=0.045±0.016 min-1 and KPatlak=0.039±0.013 min-1. After treatment, these values were SUV=0.74±0.19, KFLT=0.011±0.005 min-1 and KPatlak=0.005±0.002 min-1. Compartmental analysis revealed a significant drop in k3 in irradiated cervical marrow. FLT uptake in the bone marrow outside the radiation field exhibited a significantly smaller decrease. Conclusions: There is a marked decrease in FLT uptake in irradiated bone marrow after 10 Gy of radiation therapy to the head and neck. The drop in FLT uptake in irradiated marrow is due to a significant decrease in the net phosphorylation rate of FLT.",

keywords = "3′-Deoxy-3′-[F]fluorothymidine, Bone marrow, Chemoradiation, FLT",

author = "Yusuf Menda and {Boles Ponto}, {Laura L.} and Dornfeld, {Kenneth J.} and Tewson, {Timothy J.} and Watkins, {G. Leonard} and Gupta, {Anjali K.} and Carryn Anderson and Sarah McGuire and Schultz, {Michael K.} and Sunderland, {John J.} and Graham, {Michael M.} and Buatti, {John M.}",

note = "Funding Information: This research was funded, in part, by National Institutes of Health grant 1R21 CA130281-01 and a University of Iowa Carver College of Medicine and Holden Comprehensive Cancer Center grant. The authors would like to acknowledge the support and efforts of the technical staff of the University of Iowa PET Imaging Center (John Richmond, Dean Clermont, Christine Mundt, Julie Riggert, Beth Johnson, Kelli Schlarbaum and Beth Schmitt), our research nurses Jo Clark and Jane Hershberger, and our clinical research coordinator Kellie Bodeker-Goranson (Department of Radiation Oncology).",

year = "2010",

month = may,

doi = "10.1016/j.nucmedbio.2010.02.005",

language = "English (US)",

volume = "37",

pages = "433--438",

journal = "Nuclear Medicine and Biology",

issn = "0969-8051",

publisher = "Elsevier Inc.",

number = "4",

}

TY - JOUR

T1 - Investigation of the pharmacokinetics of 3′-deoxy-3′-[18F]fluorothymidine uptake in the bone marrow before and early after initiation of chemoradiation therapy in head and neck cancer

AU - Menda, Yusuf

AU - Boles Ponto, Laura L.

AU - Dornfeld, Kenneth J.

AU - Tewson, Timothy J.

AU - Watkins, G. Leonard

AU - Gupta, Anjali K.

AU - Anderson, Carryn

AU - McGuire, Sarah

AU - Schultz, Michael K.

AU - Sunderland, John J.

AU - Graham, Michael M.

AU - Buatti, John M.

N1 - Funding Information: This research was funded, in part, by National Institutes of Health grant 1R21 CA130281-01 and a University of Iowa Carver College of Medicine and Holden Comprehensive Cancer Center grant. The authors would like to acknowledge the support and efforts of the technical staff of the University of Iowa PET Imaging Center (John Richmond, Dean Clermont, Christine Mundt, Julie Riggert, Beth Johnson, Kelli Schlarbaum and Beth Schmitt), our research nurses Jo Clark and Jane Hershberger, and our clinical research coordinator Kellie Bodeker-Goranson (Department of Radiation Oncology).

PY - 2010/5

Y1 - 2010/5

N2 - Introduction: The kinetics of the bone marrow uptake of 3'-deoxy-3'-[18F]fluorothymidine (FLT) before and early after initiation of chemoradiation therapy was investigated in patients with head and neck cancer. Methods: Fourteen subjects with head and neck cancer underwent FLT positron emission tomography (PET) at baseline and after 10 Gy of radiation therapy. Thirteen subjects also received one cycle of platinum-based chemotherapy before the second FLT PET. Kinetic parameters, including the flux constant based on compartmental analysis (KFLT) and the Patlak constant (KPatlak) for cervical marrow, were calculated. Standardized uptake values (SUVs) for the cervical marrow (inside the radiation field) and lumbar spine marrow (outside the radiation field) were also determined. Results: There was a significant drop in FLT uptake in the bone marrow inside the radiation field. Mean pretreatment uptake values for the cervical spine were SUV=3.08±0.66, KFLT=0.045±0.016 min-1 and KPatlak=0.039±0.013 min-1. After treatment, these values were SUV=0.74±0.19, KFLT=0.011±0.005 min-1 and KPatlak=0.005±0.002 min-1. Compartmental analysis revealed a significant drop in k3 in irradiated cervical marrow. FLT uptake in the bone marrow outside the radiation field exhibited a significantly smaller decrease. Conclusions: There is a marked decrease in FLT uptake in irradiated bone marrow after 10 Gy of radiation therapy to the head and neck. The drop in FLT uptake in irradiated marrow is due to a significant decrease in the net phosphorylation rate of FLT.

AB - Introduction: The kinetics of the bone marrow uptake of 3'-deoxy-3'-[18F]fluorothymidine (FLT) before and early after initiation of chemoradiation therapy was investigated in patients with head and neck cancer. Methods: Fourteen subjects with head and neck cancer underwent FLT positron emission tomography (PET) at baseline and after 10 Gy of radiation therapy. Thirteen subjects also received one cycle of platinum-based chemotherapy before the second FLT PET. Kinetic parameters, including the flux constant based on compartmental analysis (KFLT) and the Patlak constant (KPatlak) for cervical marrow, were calculated. Standardized uptake values (SUVs) for the cervical marrow (inside the radiation field) and lumbar spine marrow (outside the radiation field) were also determined. Results: There was a significant drop in FLT uptake in the bone marrow inside the radiation field. Mean pretreatment uptake values for the cervical spine were SUV=3.08±0.66, KFLT=0.045±0.016 min-1 and KPatlak=0.039±0.013 min-1. After treatment, these values were SUV=0.74±0.19, KFLT=0.011±0.005 min-1 and KPatlak=0.005±0.002 min-1. Compartmental analysis revealed a significant drop in k3 in irradiated cervical marrow. FLT uptake in the bone marrow outside the radiation field exhibited a significantly smaller decrease. Conclusions: There is a marked decrease in FLT uptake in irradiated bone marrow after 10 Gy of radiation therapy to the head and neck. The drop in FLT uptake in irradiated marrow is due to a significant decrease in the net phosphorylation rate of FLT.

KW - 3′-Deoxy-3′-[F]fluorothymidine

KW - Bone marrow

KW - Chemoradiation

KW - FLT

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